Meeting Abstract

4-1  Thursday, Jan. 5 08:00 - 08:15  Optimal muscle length is the same for twitch and tetanic contractions in muscles from mdm mice: a role for titin in isometric force production? HESSEL, AL*; NISHIKAWA, KC; Northern Arizona University; Northern Arizona University alh385@nau.edu https://alhlabbench.wordpress.com/

The muscular dystrophy with myositis (mdm) mutation in mouse is a spontaneous deletion in the I-band portion of the titin gene. I-band titin is elastic and connects myosin to the Z-disk. Mechanical tests of mdm muscles and myofibrils during stretch demonstrate that residual force enhancement is reduced, suggesting a critical role for titin during eccentric contraction. From this line of research, a new mechanism of muscle contraction, the winding filament hypothesis (WFH), was proposed. The WFH adds a role for titin into the sliding filament theory and predicts that during muscle activation, titin binds to and winds upon the thin filaments. The hypothesis suggests that titin stiffness is increased both by titin winding due to cross bridge rotation of the thin filaments and by external forces that stretch the sarcomere. It remains unclear why mdm muscles exhibit reduced isometric stress. We used twitch and tetanic contractions in wildtype and mdm muscles to characterize the length dependence of isometric force production. Results show that decreased isometric stress in mdm is muscle-specific, and that mdm muscles produce maximum force at the same length during twitch and tetanic stimulation. In contrast, it is well documented that maximum tetanic stress is produced at a shorter muscle length than maximal twitch stress in wild-type muscles. Under the WFH, the twitch contraction would lead to titin binding but not allow time for complete winding, and thus would produce a compliant titin compared to a tetanic contraction. The longer optimal length for twitch suggests a that titin stiffness may contribute to active force production. However, if mdm titin fails to bind to thin filaments, then titin stiffness should be similar and both contractions would thus have similar optimal lengths.